Background. Patients with dengue can experience a variety of serious complications including hypovolemic shock, thrombocytopenia, and bleeding. These problems occur as plasma viremia is resolving and ...are thought to be immunologically mediated. Early corticosteroid therapy may prevent the development of such complications but could also prolong viral clearance. Methods. We performed a randomized, placebo-controlled, blinded trial of low-dose (0.5 mg/kg) or high-dose (2 mg/kg) oral prednisolone therapy for 3 days in Vietnamese patients aged 5–20 years admitted with dengue and fever for ≤72 hours, aiming to assess potential harms from steroid use during the viremic phase. Intention-to-treat analysis was performed using linear trend tests with a range of clinical and virological endpoints specified in advance. In addition to recognized complications of dengue, we focused on the are under the curve for serial plasma viremia measurements and the number of days after enrollment to negative viremia and dengue nonstructural protein 1 status. Results. Between August 2009 and January 2011, 225 participants were randomized to 1 of the 3 treatment arms. Baseline characteristics were similar across the groups. All patients recovered fully and adverse events were infrequent. Aside from a trend toward hyperglycemia in the steroid recipients, we found no association between treatment allocation and any of the predefined clinical, hematological, or virological endpoints. Conclusions. Use of oral prednisolone during the early acute phase of dengue infection was not associated with prolongation of viremia or other adverse effects. Although not powered to assess efficacy, we found no reduction in the development of shock or other recognized complications of dengue virus infection in this study. Clinical Trials Registration. ISRCTN39575233.
We have conducted a systematic survey for the X-ray properties of millisecond pulsars (MSPs). Currently, there are 47 MSPs with confirmed X-ray detections. We have also placed the upper limits for ...the X-ray emission from the other 36 MSPs by using the archival data. We have normalized their X-ray luminosities Lx and their effective photon indices Γ into a homogeneous data set, which enables us to carry out a detailed statistical analysis. Based on our censored sample, we report a relation of L x 10 31.05 ( E ˙ 10 35 ) 1.31 erg s−1 (2-10 keV) for the MSPs. The inferred X-ray conversion efficiency is found to be lower than the previously reported estimate that could be affected by selection bias. Lx also correlates/anti-correlates with the magnetic field strength at the light cylinder BLC/characteristic age τ. On the other hand, there is no correlation between Lx and their surface magnetic field strength Bs. We have further divided the sample into four classes: (i) black-widows, (ii) redbacks, (iii) isolated MSPs, and (iv) other MSP binaries, and compare the properties among them. We noted that while the rotational parameters and the orbital periods of redbacks and black-widows are similar, Lx of redbacks are significantly higher than those of black-widows in the 2-10 keV band. Also the Γ of redbacks are apparently smaller than those of black-widows, which indicates that the X-ray emission of redbacks are harder than that of black-widows. This can be explained by the different contribution of intrabinary shocks in the X-ray emission of these two classes.
We examined the associations of GAD antibodies (GADA) and C-peptide (CP) with insulin initiation, glycemic responses, and severe hypoglycemia in type 2 diabetes (T2D).
In 5,230 Chinese patients ...(47.6% men) with T2D (mean ± SD age: 56.5 ± 13.9 years; median diabetes duration: 6 interquartile range 1, 12 years), enrolled consecutively in 1996-2012 and prospectively observed until 2019, we retrospectively measured fasting CP and GADA in stored serum and examined their associations with aforementioned outcomes.
At baseline, 28.6% (n = 1,494) had low CP (<200 pmol/L) and 4.9% (n = 257) had positive GADA (GADA+). In the low-CP group, 8.0% had GADA+, and, in the GADA+ group, 46.3% had low CP. The GADA+ group had an adjusted hazard ratio (aHR) of 1.46 (95% CI 1.15-1.84, P = 0.002) for insulin initiation versus the GADA- group, while the low-CP group had an aHR of 0.88 (0.77-1.00, P = 0.051) versus the high-CP group. Following insulin initiation, the GADA+ plus low-CP group had the largest decrements in HbA1c (-1.9% at month 6; -1.5% at month 12 vs. -1% in the other three groups). The aHR of severe hypoglycemia was 1.29 (95% CI 1.10-1.52, P = 0.002) in the low-CP group and 1.38 (95% CI 1.04-1.83, P = 0.024) in the GADA+ group.
There is considerable heterogeneity in autoimmunity and β-cell dysfunction in T2D with GADA+ and high CP associated with early insulin initiation, while GADA+ and low CP, increased the risk of severe hypoglycemia. Extended phenotyping is warranted to increase the precision of classification and treatment in T2D.
We present the results of a detailed investigation of the prompt and afterglow emission in the High Energy Stereoscopic System (H.E.S.S.)-detected GRB 190829A. Swift and Fermi observations of the ...prompt phase of this gamma-ray burst (GRB) reveal two isolated subbursts or episodes, separated by a quiescent phase. The energetic and the spectral properties of the first episode are in stark contrast to the second. The first episode, which has a higher spectral peak ∼120 keV and a low isotropic energy ∼1050 erg is an outlier to the Amati correlation and marginally satisfies the Yonetoku correlation. However, the energetically dominant second episode has lower peak energy and is consistent with the above correlations. We compared this GRB to other low-luminosity GRBs (LLGRBs). Prompt emission of LLGRBs also indicates a relativistic shock breakout origin of the radiation. For GRB 190829A, some of the properties of a shock breakout origin are satisfied. However, the absence of an accompanying thermal component and energy above the shock breakout critical limit precludes a shock breakout origin. In the afterglow, an unusual long-lasting late-time flare of duration ∼104 s is observed. We also analyzed the late-time Fermi Large Area Telescope (LAT) emission that encapsulates the H.E.S.S. detection. Some of the LAT photons are likely to be associated with the source. All of the above observational facts suggest GRB 190829A is a peculiar low-luminosity GRB that is not powered by a shock breakout, and has an unusual rebrightening due to patchy emission or a refreshed shock during the afterglow. Furthermore, our results show that teraelectronvolt-energy photons seem common in both high-luminosity GRBs and LLGRBs.
Recent observations strongly suggest that the millisecond pulsar binary PSR J1023+0038 has developed an accretion disk since 2013 June. We present a multi-wavelength analysis of PSR J1023+0038, which ...reveals that (1) its gamma-rays suddenly brightened within a few days in 2013 June/July and has remained at a high gamma-ray state for several months; (2) both UV and X-ray fluxes have increased by roughly an order of magnitude; and (3) the spectral energy distribution has changed significantly after the gamma-ray sudden flux change. Time variabilities associated with UV and X-rays are on the order of 100-500 s and 50-100 s, respectively. Our model suggests that a newly formed accretion disk, due to the sudden increase of the stellar wind, could explain the changes of all these observed features. The increase of UV is emitted from the disk, and a new component in gamma-rays is produced by inverse Compton scattering between the new UV component and pulsar wind. The increase of X-rays results from the enhancement of injection pulsar wind energy into the intra-binary shock due to the increase of the stellar wind. We also predict that the radio pulses may be blocked by the evaporated winds from the disk, and the pulsar is still powered by rotation.
Leukocyte telomere length (LTL) is suggested to be a biomarker of biological age and reported to be associated with metabolic diseases such as type 2 diabetes. Glucose metabolic traits including ...glucose and insulin levels have been reported to be associated with LTL in adulthood. However, there is relatively little research focusing on children's LTL and the association with prenatal exposures. This study investigates the relationship between maternal and offspring glucose metabolism with offspring LTL in early life.
This study included 882 mother-child pairs from the HAPO Hong Kong Field Centre, with children evaluated at age 7.0 ± 0.4 (mean ± SD) years. Glucose metabolic traits including maternal post-load glucose during pregnancy, children's glucose and insulin levels, and their derived indices at follow-up were measured or calculated. Offspring LTL was assessed using real-time polymerase chain reaction.
Sex- and age-adjusted children's LTL was found to be associated with children's HOMA-IR (β=-0.046 ± 0.016, p=0.005). Interestingly, both children's and maternal post-load glucose levels were positively associated with children's LTL. However, negative associations were observed between children's LTL and children's OGTT insulin levels. In addition, the LTL in females was more strongly associated with pancreatic beta-cell function whilst LTL in males was more strongly associated with OGTT glucose levels.
Our findings suggest a close association between maternal and offspring glucose metabolic traits with early life LTL, with the offspring sex as an important modifier of the disparate relationships in insulin production and response.
The first measurements from the CIBER experiment of extragalactic background light (EBL) in near-infrared (NIR) band exhibit a higher intensity than those inferred through γ-ray observations. Recent ...theoretical-EBL intensities are typically consistent with the very high energy (VHE) γ-ray observations. Yet, it is possible that the excess NIR radiation is a new component of EBL and not in tension with the TeV spectra of distant blazars, since the hypothetical axionlike particle (ALP) may lead to a reduced opacity of the Universe for VHE γ-rays. In order to probe whether the excess component arises mainly from EBL, thirteen observed spectra in high energy and VHE ranges from ten distant TeV BL Lac objects are fitted by four theoretical spectra which involve theoretical EBL (Gilmore et al.), Gilmore's EBL model including photon/ALP coupling, Gilmore's EBL with CIBER excess and the latter including photon/ALP coupling respectively. We find the goodness of fit for the model with CIBER excess can be improved with a significance of 7.6σ after including the photon/ALP coupling. Thus, the ALP/photon mixing mechanism can effectively alleviate the tension; However, the Gilmore EBL model, on the whole, is more compatible with the observed spectra compared to those with ALP, although individual blazars such as PKS 1424 + 240 and 1ES 1101-232 prefer the ALP-model. Our results suggest that the recent EBL models can solely explain the VHE γ-ray observations, and assuming the existence of the ALP to alleviate the tension is not required in a statistical sense, thus the excess over the EBL models is less likely to be a new EBL component.
Several studies support potential links between relative leukocyte telomere length (rLTL), a biomarker of biological aging, and type 2 diabetes. This study investigates relationships between rLTL and ...incident cardiovascular disease (CVD) in patients with type 2 diabetes.
Consecutive Chinese patients with type 2 diabetes (
= 5,349) from the Hong Kong Diabetes Register for whom DNA obtained at baseline was stored and follow-up data were available were studied. rLTL was measured by using quantitative PCR. CVD was diagnosed on the basis of ICD-9 code.
Mean follow-up was 13.4 years (SD 5.5 years). rLTL was correlated inversely with age, diabetes duration, blood pressure, HbA
, and urine albumin-to-creatinine ratio (ACR), and positively with estimated glomerular filtration rate (eGFR) (all
< 0.001). Subjects with CVD at baseline had a shorter rLTL (4.3 ± 1.2 ΔΔCt) than did subjects without CVD (4.6 ± 1.2 ΔΔCt) (
< 0.001). Of the 4,541 CVD-free subjects at baseline, the 1,140 who developed CVD during follow-up had a shorter rLTL (4.3 ± 1.2 ΔΔCt) than those who remained CVD-free after adjusting for age, sex, smoking, and albuminuria status (4.7 ± 1.2 ΔΔCt) (
< 0.001). In Cox regression models, shorter rLTL was associated with higher risk of incident CVD (for each unit decrease, hazard ratio 1.252 95% CI 1.195-1.311,
< 0.001), which remained significant after adjusting for age, sex, BMI, systolic blood pressure, LDL cholesterol, HbA
, eGFR, and ACR (hazard ratio 1.141 95% CI 1.084-1.200,
< 0.001).
rLTL is significantly shorter in patients with type 2 diabetes and CVD, is associated with cardiometabolic risk factors, and is independently associated with incident CVD. Telomere length may be a useful biomarker for CVD risk in patients with type 2 diabetes.
GeV flares from PSR B1259−63/LS 2883 were seen starting around 30 days after the two periastron passages in 2010 and 2014. The flares are clearly delayed compared to the occurrence of the X-ray and ...TeV flux peaks during the post-periastron disk crossing. Although several attempts have been put forward to explain this phenomenon, the origin of these GeV flares remains a puzzle. Here we present a detailed analysis of the observational data taken by the Fermi and Swift observatories over the 2017 September periastron passage. For the first time, we find short-lived but powerful GeV flares on timescales of down to three hours. The onset of the GeV flaring period in 2017 is also delayed compared to that seen in 2011 and 2014. Supplemented by a reanalysis of previous data, we compare the Fermi/LAT, Swift/XRT, and Swift/UVOT light curves in 2017 with those taken over the 2010 and 2014 periastrons, and differences in UVOT light curves are noted.
We report the analysis result of UV/X-ray emission from AR Scorpii, which is an intermediate polar (IP) composed of a magnetic white dwarf and an M-type star, with the XMM-Newton data. The X-ray/UV ...emission clearly shows a large variation over the orbit, and their intensity maximum (or minimum) is located at the superior conjunction (or inferior conjunction) of the M star orbit. The hardness ratio of the X-ray emission shows a small variation over the orbital phase and shows no indication of the absorption by an accretion column. These properties are naturally explained by the emission from the M star surface rather than that from the accretion column on the white dwarf's (WD) star, which is similar to usual IPs. Additionally, the observed X-ray emission also modulates with the WD's spin with a pulse fraction of ∼14%. The peak position is aligned in the optical/UV/X-ray band. This supports the hypothesis that the electrons in AR Scorpii are accelerated to a relativistic speed and emit non-thermal photons via the synchrotron radiation. In the X-ray bands, evidence of the power-law spectrum is found in the pulsed component, although the observed emission is dominated by the optically thin thermal plasma emissions with several different temperatures. It is considered that the magnetic dissipation/reconnection process on the M star surface heats up the plasma to a temperature of several keV and also accelerates the electrons to the relativistic speed. The relativistic electrons are trapped in the WD's closed magnetic field lines by the magnetic mirror effect. In this model, the observed pulsed component is explained by the emissions from the first magnetic mirror point.